title: In vitro time-kill experiments with besifloxacin, moxifloxacin and gatifloxacin in the absence and presence of benzalkonium chloride.
abstract: OBJECTIVE
  To compare the bactericidal activity of besifloxacin, moxifloxacin and gatifloxacin and determine the contribution of the preservative benzalkonium chloride (BAK) to bactericidal activity.
  
  
  METHODS
  Time-kill experiments were performed against four species (n=12) with besifloxacin, moxifloxacin and gatifloxacin, in the presence or absence of BAK, at t=0, 5, 15, 30, 45, 60, 120 and 360 min, according to standard CLSI methods.
  
  
  RESULTS
  In the presence of BAK, bactericidal activity was observed within 5 min, regardless of the fluoroquinolone tested. The bactericidal activity of BAK was unaffected by the concurrent presence of besifloxacin and rapid killing (within 5 to 15 min) was not observed at BAK concentrations below 50 mg/L. However, when tested without BAK, besifloxacin was bactericidal in as little as 45 min, while moxifloxacin and gatifloxacin required at least 120 min; besifloxacin kill rates against fluoroquinolone-susceptible and -resistant strains were at least 2- to 4-fold faster than those of gatifloxacin or moxifloxacin.
  
  
  CONCLUSIONS
  Besifloxacin was the most rapidly bactericidal fluoroquinolone tested, followed by gatifloxacin and moxifloxacin, both of which had similar activity. Our studies demonstrate that the previously reported rapid in vitro killing by gatifloxacin formulations was probably due to the concurrent presence of 50 mg/L BAK, which is much higher than the 3.2 mg/L BAK observed in human tears 1 min after instillation of ophthalmic gatifloxacin solutions [Friedlaender MH, Breshears D, Amoozgar B et al. The dilution of benzalkonium chloride (BAK) in the tear film. Adv Ther 2006; 23: 835-41].
authors.affiliation: Bausch & Lomb, Inc., Rochester, NY 14609, USA. wolfgang.haas@bausch.com
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Haas
authors.forename: Chris M
authors.initials: CM
authors.lastname: Pillar
authors.forename: Christine K
authors.initials: CK
authors.lastname: Hesje
authors.forename: Christine M
authors.initials: CM
authors.lastname: Sanfilippo
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Morris
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001548:Benzalkonium Compounds / Q000494:pharmacology; D004347:Drug Interactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D050296:Microbial Viability / Q000187:drug effects*; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001381:Azepines; D001548:Benzalkonium Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C522124:besifloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin